Pressure sensing system and method

ABSTRACT

A device for detecting rhinitis in a human subject includes an inflatable member that, in a first state, is configured to be introducible into the nasal cavity of the human subject; an expansion member configured to expand the inflatable member to an expanded, second state within the nasal cavity such that the inflatable member abuts against the tissue of the nasal cavity, and a pressure sensing member configured to measure a pressure exerted on the inflatable member by the tissue of the nasal cavity. A system for detecting rhinitis and methods for analyzing tissue response pressure, detecting rhinitis, predicting the efficacy of a planned rhinitis treatment and evaluating the efficacy of a previous rhinitis treatment are provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §119(e) to U.S.Provisional Application No. 61/576,804, filed on Dec. 16, 2011. Thisapplication also claims priority under 35 U.S.C. §119(a) to ApplicationNo. 11194062.3, filed in Europe on Dec. 16, 2011. The entirety of eachof the above-identified applications is expressly incorporated herein byreference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to devices, systems and methods fordetecting rhinitis. The present invention moreover relates to methodsfor predicting the efficacy of a rhinitis treatment to be performed, aswell as to methods for evaluating the efficacy of a previously performedrhinitis treatment

2. Description of Background Art

Rhinitis, commonly referred to as a stuffy nose, can generally becategorized into two groups: allergic rhinitis and non-allergicrhinitis. Differentiating allergic rhinitis from other causes ofrhinitis can be difficult because the diagnostic criteria for variousforms of rhinitis are not always clear-cut. Accurate diagnosis ishowever important because therapies that are effective for allergicrhinitis (i.e. antihistamines and nasal corticosteroids) may be lesseffective for other types of rhinitis. Allergic rhinitis includesepisodic rhinitis; occupational rhinitis (allergen); perennial rhinitisand seasonal rhinitis. Non-allergic rhinitis includes atrophic rhinitis;chemical- or irritant-induced rhinitis; drug-induced rhinitis such asinduced by antihypertensive medications, aspirin, non-steroidalanti-inflammatory drugs and oral contraceptives, and rhinitismedicamentosa; emotional rhinitis; exercise-induced rhinitis; gustatoryrhinitis; hormone-induced rhinitis such as induced by hypothyroidism,menstrual cycle, oral contraceptives and pregnancy; infectious rhinitissuch as acute (usually viral) rhinitis, chronic (rhino sinusitis);non-allergic rhinitis with eosinophilia syndrome; occupational rhinitis(irritant); perennial non-allergic rhinitis such as vasomotor rhinitis;postural reflexes primary ciliary dyskinesia, and reflux-inducedrhinitis or gastroesophageal reflux disease. If the patient has severesymptoms or an unclear diagnosis, or if he or she is a potentialcandidate for allergen avoidance treatment or immunotherapy, an allergytest should be performed. A comprehensive history and physicalexamination should however be used to help diagnose the cause ofrhinitis.

Different methods are known for generally studying nasal patency, i.e.nasal openness and/or airflow, without necessarily resulting indiagnosis. Malm lists a number of these methods (Maim, L., Allergy,1997; 52:19-23), which include computed tomography, magnetic resonanceimaging, volumetry, rhino stereometry, acoustic rhinometry,rhinomanometry and nasal peak flow.

Devices and methods are known for generally measuring an inner diameterof a body lumen, such as the devices and methods disclosed in U.S.Application Publication No. 2010/0234840. The method includes insertinga balloon in a body lumen, such as the esophagus, inflating the ballooninside the body lumen using an expansion medium; and monitoring a massof the expansion medium inside the balloon. Wall compliance of anesophagus can moreover be determined by measuring the total fluid withinthe balloon at two different static pressures and calculating the wallcompliance based on the variation in fluid between the first and thesecond static pressure.

In WO 2004/047675 there are disclosed devices and methods for measuringchanges in tissue elasticity. The disclosed device includes a catheterwith an expandable element at a proximal end. The catheter is movedlongitudinally and circumferentially within a cavity such as an arteryand changes in elasticity are detected by measuring changes in pressure.The catheter may be further equipped with sensors for measuringtemperature and pH. This method is described to be useful forcharacterizing vulnerable plaque and cancer tissue.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide novel devices andsystems for detecting rhinitis. It is moreover an object of the presentinvention to provide novel devices, systems and methods for detectingrhinitis, predicting the efficacy of a planned rhinitis treatment andevaluating the efficacy of a previous rhinitis treatment.

In a first aspect of the invention, there is provided a device fordetecting rhinitis in a human subject, comprising: an inflatable memberthat, in a first state, is configured to be introducible into the nasalcavity of the human subject; an expansion member configured to expandthe inflatable member to an expanded, second state within the nasalcavity such that the inflatable member abuts against the tissue of thenasal cavity; and a pressure sensing member configured to measure apressure exerted on the inflatable member by the tissue of the nasalcavity. The expansion member may comprise a tubular structure comprisingan end portion arranged freely within said inflatable member andcomprising at least one opening for fluid communication with theinflatable member.

By introducing and expanding the inflatable member into the nasal cavityof a human subject, a pressure is applied onto the tissue. Both healthysubjects and subjects suffering from a form of rhinitis respond to theapplied pressure. The response to the applied pressure is monitored bythe pressure sensing member as changes in the pressure exerted on theinflatable member by the tissue over a period of time. In both healthysubjects and subjects suffering from rhinitis, a steep decrease in themeasured pressure is initially observed. Thereafter, sudden pressuredecreases are observed in all subjects until a saturation pressure isreached. In between the pressure decreases, there are periods of nearlyconstant pressure. These pressure decreases are believed to correspondto sphincters opening up and, as a consequence, a corresponding decreasein blood filling of the nasal mucosa. When the abovementioned saturationpressure is reached, the applied pressure may be reduced. This leads toa smooth recovery in the measured pressure to a second saturationpressure. This is believed to correspond to refilling of the vessels andresumed function of the sphincters.

It has been found by the inventors that the tissue response pressure inthe nasal cavity over time is different in a subject suffering fromrhinitis than in a healthy subject. By measuring the tissue responsepressure over time with a device according to the first aspect of thepresent invention, rhinitis may consequently be detected. In addition,the device may be used for evaluating the efficacy of a previouslyperformed rhinitis treatment, i.e. for evaluating whether or not apatient has been cured from his/her rhinitis or whether the symptomshave been alleviated. The device may moreover be used for predictingefficacy of a planned rhinitis treatment, i.e. for predicting e.g. theprobability of a certain patient responding to the treatment.

For detecting, evaluating and predicting as described above, it may beuseful to create a measured tissue response pressure curve reflectingthe changes in measured tissue response pressure over time, and tocompare that measured pressure curve to a reference pressure curve,reflecting for example the changes in tissue response pressure over timein the nasal cavity of a healthy human subject.

The tissue response to an applied static pressure, e.g. as exerted onthe inflatable member as described above, is herein generally referredto as a measured pressure or a tissue response pressure.Correspondingly, a curve reflecting the changes in measured tissueresponse pressure over time is herein generally referred to as ameasured pressure curve. The pressure exerted by tissue onto theinflatable member can be measured as the pressure within the inflatablemember in embodiments wherein the circumference of the inflatable memberdefines an inner chamber. Such a pressure is referred to as the innerpressure of the inflatable member.

In another embodiment of the first aspect, there is provided a devicewherein said inflatable member in the second state is configured to abutagainst the tissue of the nasal cavity at a pressure of betweenapproximately 100 and 180 mbar. This pressure represents the initiallyapplied pressure on the tissue. As discussed above, the application of aspecific pressure onto the tissue in the nasal cavity influences thenasal tissue in a specific way which is reflected in tissue responsepressure as measured by the pressure sensing member. The initiallyapplied pressure may lie in the range of from 120 to 160 mbar, such asfrom 130 to 150 mbar. In some cases, the applied pressure may be 140mbar.

The pressure sensing member may for instance be positioned within theinflatable member, such that the inflatable member comprises at least aportion of the pressure sensing member. Such a pressure sensing membermay for example be located on the surface of the inflatable member.

The device may further comprise a display member configured to displaythe pressure measured by the pressure sensing member, i.e. the tissueresponse pressure. A display member, such as an LCD panel, facilitatesmonitoring of the tissue response pressure by an operator. Such displaymay either show a current value of the tissue response pressure only, ormay alternatively or also show how the tissue response pressure developsover time. In other words, the display member is in one embodimentconfigured to display the pressure measured by the pressure sensingmember as a function of time. The display member may be digital oranalog. In case the display member only shows a current value of thetissue response pressure, the operator has to monitor the timedevelopment of the signal in order to be able to draw any conclusionsregarding the nasal pathology. If the development of the tissue responsepressure over time is shown, e.g. on a computer screen or on anXY-plotter, the evaluation of nasal pathology for the operator isfacilitated. In both cases however, it is the operator who, based onexperience and/or training, draws conclusions regarding the health ofthe patient.

In another embodiment of the first aspect, the expansion membercomprises a pressure generator for increasing the pressure within theinflatable member, and a closing valve. The closing valve is used toform a closed system of the inflatable member and at least a part of theexpansion member when the desired pressure has been applied.Furthermore, the pressure sensing member may be arranged externally ofand/or separately from the stimulation member, for example such that itis integrated with the expansion member, while being configured tomeasure the internal air pressure in the closed system.

In another embodiment of the first aspect, the inflatable member isconnectable to a vibration generating member which is configured tobring the inflatable member to vibrate such that vibrations are impartedto the tissue of the nasal cavity. Vibrations may be imparted to thenasal tissue for different purposes. Not only may vibrations be appliedfor treatment of the nasal mucosa, but also for studying tissuecompliance. Monitoring changes in measured tissue pressure duringvibration stimulation in the nasal cavity may give an indication of theprogress of vibration treatment, and possibly recovery of the nasaltissue, as well as an estimate of tissue compliance.

In another aspect of the present invention, there is provided a systemfor detecting rhinitis, comprising: a data collection module configuredto obtain an input signal reflecting a tissue response pressure of thenasal cavity of a human subject; a pressure analyzing module configuredto analyze said input signal to identify plateaus and decreases in thesignal over a period of time; and a rhinitis detection module configuredto detect rhinitis by comparing said plateaus and decreases in thesignal over time with at least one predetermined boundary condition.

The rhinitis detecting system of the second aspect may be used fordetecting rhinitis in a human subject, and, in similarity to the abovedefined device, be useful for predicting the efficacy of a plannedrhinitis treatment as well as for evaluating the efficacy of apreviously conducted rhinitis treatment.

The data collection module is arranged to obtain an input signalreflecting a tissue response pressure and to collect the individualvalues of the input signal over time. The pressure analyzing moduleanalyzes the signal in order to identify changes. Such changes arepressure plateaus and decreases, whereas the pressure plateauscorrespond to periods of nearly constant pressure in between thepressure decreases as discussed in connection with the device aspect.The collected tissue response pressure of a human subject exhibitspressure plateaus and decreases that are characteristic for the healthcondition of the human subject in question. Thus, the pressure plateausand decreases corresponding to a certain patient suffering from rhinitisare different from those of a healthy subject. This enables detection ofrhinitis by comparing the plateaus and decreases of a certain humansubject with a boundary condition.

A boundary condition may for example correspond to a calculated value oran average value obtained from a number of measurements of tissueresponse pressure. Non-limiting examples of boundary conditions usefulfor the detection of rhinitis are, among others, a tissue responsepressure corresponding to a final saturation plateau, a slope of aspecific decrease in tissue response pressure, a length of a specifictissue response plateau, a tissue response pressure obtained after apredetermined period of time, the time period for reaching apredetermined pressure plateau, the number of pressure decreases beforereaching a saturation pressure and the number of plateaus beforereaching a saturation pressure. In one example, the system according tothe present invention may further comprise a boundary determining moduleconfigured to determine from at least one reference pressure curve atleast one boundary condition.

In another embodiment, the pressure analyzing module is configured tocharacterize said plateaus and decreases of the signal by at least onecurve property selected from amplitude, rate of change and frequency.The amplitude here refers to the length of the pressure decreases,expressed in pressure units or in time. The rate of change is the slopeof the decreases, whereas the frequency refers to the number ofdecreases per time unit. By definition of such specific curveproperties, the detection of rhinitis can be made easier. The tissueresponse pressure curve of a healthy subject typically demonstrates adistinctive number of decreases and plateaus before reaching a finalsaturation pressure, whereas the tissue response pressure curves ofsubjects suffering from different forms of rhinitis typicallydemonstrate either a higher number of decreases and plateaus or a lowernumber of decreases and plateaus. Correspondingly, the curve propertiesof a tissue response pressure curve of a healthy subject may bedistinguished from the curve properties of tissue response pressurecurves of subjects suffering from rhinitis. The curve properties of themeasured tissue response pressure curve may consequently be compared tospecific boundary conditions for detection of rhinitis. Non-limitingexamples of boundary conditions specific for the curve propertiesamplitude, rate of change and frequency are a maximum threshold(threshold_(max)) for a specific curve property and a minimum threshold(threshold_(min)) for a specific curve property. Thus, in anotherembodiment, the rhinitis detection module is configured to detect afirst and second subtype of rhinitis by finding portions of at least oneof the curve properties having individual values above a predeterminedthreshold_(max) for that particular curve property to detect a firstsubtype of rhinitis, and by finding portions of at least one of thecurve properties having individual values below a predeterminedthreshold_(min) for that particular curve property to detect a secondsubtype of rhinitis.

The pressure analyzing module thus has the capability to detect theabove mentioned features of the input signal. In addition, the pressureanalyzing module may have further processing capability which may allowthe module to recognize and compare curve patterns.

In yet another embodiment, the pressure analyzing module is furtherconfigured to detect peaks corresponding to sneezes in the input signal.Imparting vibrations to the nasal cavity may provoke sneezing. Suchsneezes are registered as peaks in the measured tissue responsepressure. The frequency of sneezes can give further indication of thehealth condition of the human subject in question.

The input signal reflecting a tissue response pressure of the nasalcavity of a human subject corresponds, in another embodiment, to thepressure exerted by tissue of the nasal cavity on a device according tothe definition in connection with the first aspect of the presentinvention. More specifically, the tissue response pressure maycorrespond to the pressure exerted on a device connectable to avibration generating member. Thus, the input signal reflects a tissuepressure influenced by vibrations as exerted on a vibrating inflatablemember. Such an example system may further comprise a compliancedetermining module configured to determine the compliance of the tissueto imparted vibrations. As used herein, the term compliance refers to ameasure of the tendency of the nasal cavity to resist recoiling towardits original dimensions upon removal of, e.g. an inflatable member andis the reciprocal of “elastance.”

In yet another embodiment of the system aspect, the system comprises adevice as defined in relation to the device aspect of the presentinvention.

In embodiments wherein the input signal reflecting a tissue responsepressure corresponds to the pressure exerted on a vibrating inflatablemember, the number of peaks in the pressure curve may be observed. Thosepeaks correspond, as previously discussed, to the human subject sneezingand may typically be observed in human subjects suffering from rhinitis.The number of peaks may thus be utilized for further specifying thesubject's health condition. The pressure analyzing module of the systemmay for instance be configured to determine whether the peak frequencysurpasses a predetermined peak threshold. When comprising a deviceaccording to the device aspect of the present invention, the system mayin addition comprise a control member configured to terminate thevibration stimulation and pressure measurement when said peak thresholdis surpassed.

The system may moreover comprise a storing module configured to store,e.g. boundary conditions, thresholds and reference curves. To facilitatepatient follow up, such a storing module may moreover enable storing oftissue response pressure curves and derived curve properties for aparticular human subject.

It should be understood that embodiments and examples described inrelation to a particular aspect of the present invention are equallyrelevant, when applicable, to the other aspects of the presentinvention.

In another aspect of the present invention, there is provided a methodfor analyzing tissue response pressure, comprising: providing a tissueresponse pressure curve reflecting the tissue response pressure of anasal cavity of a human subject over a period of time; providing areference pressure curve reflecting a reference tissue response pressureof the nasal cavity over a reference period of time; and comparing saidtissue response pressure curve with said reference pressure curve toassess correspondence between said tissue response pressure curve andreference pressure curve. This aspect of the invention is referred to asthe first method aspect of the invention.

By assessing the correspondence between a tissue response pressure curveand a reference curve, one might identify deviation from a certaincondition of a human subject as represented by the reference curve. Theanalyzing method can function as a preparatory method for identifyingdeviation prior to actually determining the condition of a humansubject. Thus, depending on the desired assessment for a particularpatient, a suitable reference curve may be provided. By comparing thedevelopment of tissue response pressure over time with a referencecurve, a lot of information on a subject's health condition canpotentially be derived, as compared to a case where only one or twotissue response pressure values are extracted. Rhinitis is a complexcondition and a lot of information may be required to enable a correctdiagnosis.

In one embodiment, the method further comprises one of: detectingrhinitis by comparing a tissue response pressure curve obtained from ahuman subject possibly suffering from rhinitis to said referencepressure curve; predicting efficacy of a rhinitis treatment by comparinga tissue response pressure curve obtained from a human subject prior torhinitis treatment to said reference pressure curve, or evaluating theefficacy of a previously performed rhinitis treatment by comparing atissue response pressure curve obtained from a human subject previouslysubjected to rhinitis treatment to said reference pressure curve. Itshould be understood that the reference pressure curve may be differentdepending on the purpose of the determination. If the comparison is madeto detect rhinitis, then the reference pressure curve may represent ahealthy condition. If the comparison is made to predict the outcome ofany planned treatment regime, the reference pressure curve may berepresentative of a health condition known to respond well to theplanned treatment in question. If the comparison on the other hand ismade to evaluate the efficacy of any previously performed rhinitistreatment, the reference pressure curve may also represent a healthycondition or correspond to a pressure response curve obtained prior tosaid treatment. It should be noted that the method may be useful forevaluating or predicting the efficacy of any previous or plannedrhinitis treatment.

Should the finding of the abovementioned method be that the humansubject suffers from rhinitis or that a previous rhinitis treatment hasnot efficiently treated the rhinitis, a rhinitis treatment may berecommended. Such rhinitis treatment is hence performed separately fromthe method of the present invention, and may for example be performed inaccordance with the method as described in WO 2008/138997, which isincorporated herein by reference and which includes vibrationstimulation of the nasal passage, among other body cavities, in order totreat, for example rhinitis.

The method according to the present invention thus provides objectivequantitative measures of the various conditions collectively referred toas rhinitis. This is lacking in the clinical practice today. Being ableto find the right diagnosis may even restrain or stop patients from(over) using inefficient medications. Furthermore, it is possible tofollow the development of the condition over time and thus to determinewhether a specific treatment is effective or not.

In another embodiment of the first method aspect, said referencepressure curve is selected from a previously obtained tissue responsepressure curve; an average of at least two previously obtained tissueresponse pressure curves; a fit of a model to at least one measuredtissue response pressure curve, and a theoretically calculated referencepressure curve. The reference pressure curve is thus selected from apredetermined reference pressure curve, but may in some instances becreated, while performing the method, from any of the above listedcurves or models. It should further be understood that the previouslyobtained tissue response pressure curves may derive from the same humansubject or from another human subject, depending on the circumstances.Further, the theoretically calculated reference pressure curve iscalculated without directly relying upon a measured tissue responsepressure, thus, it might e.g. be calculated from any known pressurecurve. A model that can be fit to measured data is a parameterizedrepresentation of the expected general shape of a tissue responsepressure curve. Use of such a model may eliminate noise from the curveand consequently make the characteristics of the curve more clear.

The comparative step of the method comprises, in another embodiment, atleast one of the following: determining that the tissue responsepressure curve corresponds to said reference pressure curve or lieswithin a predetermined tolerance interval; determining that at leastparts of the tissue response pressure curve exceed said toleranceinterval, and determining that at least parts of the tissue responsepressure curve fall below said tolerance interval. Should the tissueresponse pressure curve fall outside of the defined tolerance intervalof a healthy condition, it can, e.g. be concluded that the human subjectsuffers from rhinitis or has not been efficiently treated for his or herrhinitis. A tissue response pressure curve that at least partlysurpasses the tolerance interval may indicate a subtype of rhinitis,whereas a tissue response pressure curve that at least partly fallsbelow the tolerance interval may indicate another subtype of rhinitis.In this case, the tolerance interval may reflect a normal distributionaround a particular health condition.

In another embodiment of the method, said providing a tissue responsepressure curve is selected from obtaining time and tissue responsepressure value pairs, and fitting a model to individual values. Byfitting a model to the individual values, the comparison to a referencecurve may be easier to perform, especially if the reference curve isformulated in the same way. This can furthermore be an efficient way toremove noise from the signal.

In a further embodiment, the tissue response pressure curve is createdby collecting an input signal reflecting a tissue response pressure ofthe nasal cavity of a human subject over a period of time.

In a related aspect of the present invention, there is provided a methodfor detecting rhinitis, comprising: introducing an inflatable memberinto a nasal cavity of a human subject; expanding the inflatable memberwithin the nasal cavity such that the inflatable member abuts against atissue of the nasal cavity; measuring a pressure exerted on theinflatable member by the tissue of the nasal cavity over a period oftime to create a measured pressure curve; and analyzing the measuredpressure curve to detect rhinitis. This aspect of the invention isreferred to as the second method aspect. By using this method, aphysician can measure the nasal pathology and in an objective waydifferentiate between different forms of rhinitis. It may also bepossible to follow the development over time for a particular patient todetect long term changes in the patient's state of health.

In another related aspect of the present invention, there is provided amethod for evaluating the efficacy of a previously performed rhinitistreatment, comprising: introducing an inflatable member into a nasalcavity of a human subject; expanding the inflatable member within thenasal cavity such that the inflatable member abuts against a tissue ofthe nasal cavity; measuring a pressure exerted on the inflatable memberby the tissue of the nasal cavity over a period of time to create ameasured pressure curve; and analyzing the measured pressure curve toevaluate the efficacy of the previous rhinitis treatment. This aspect ofthe invention is referred to as the third method aspect. By using thismethod, one can determine if an administered treatment is having thedesired effect, and if not the treatment can altered, replaced, oraborted. In this way, the risk of overusing pharmaceuticals can bereduced.

In yet another related method aspect of the present invention, there isprovided a method for predicting the efficacy of a rhinitis treatment,comprising: introducing an inflatable member into a nasal cavity of ahuman subject; expanding the inflatable member within the nasal cavitysuch that the inflatable member abuts against a tissue of the nasalcavity; measuring a pressure exerted on the inflatable member by thetissue of the nasal cavity over a period of time to create a measuredpressure curve; and analyzing the measured pressure curve to predict theefficacy of rhinitis treatment. This aspect of the invention is referredto as the fourth method aspect of the invention. This method may beuseful for predicting the outcome of a specific rhinitis treatment andconsequently for selecting the most suitable treatment for a particularhuman subject.

In the following, a number of embodiments of the four method aspectswill be described.

In one embodiment, preferably relevant to the second, third and fourthmethod aspects, said analyzing comprises identifying plateaus anddecreases in said measured pressure curve, and comparing said plateausand decreases to at least one predetermined boundary condition. Thus, aspreviously discussed in connection with the system aspect, the collectedtissue response pressure from a human subject exhibits pressure plateausand decreases that are characteristic for the health condition of thesubject in question. In this manner, detection of rhinitis is enabled bycomparing the plateaus and decreases of a certain human subject with theboundary condition. The boundary condition may correspond to acalculated value or an average value obtained from a number ofmeasurements of tissue response pressure as previously discussed. Anumber of non-limiting examples of boundary conditions relevant fordetection of rhinitis are listed above. These examples of boundaryconditions are however equally relevant for predicting the efficacy of aplanned rhinitis treatment and for evaluating the efficacy of apreviously conducted rhinitis treatment. The methods may moreovercomprise determining from at least one reference pressure curve at leastone boundary condition.

In other embodiments of the method aspects, the methods may comprisecharacterizing said plateaus and decreases by at least one curveproperty selected from amplitude, rate of change and frequency. This mayenable an alternative, possibly more precise, determination of thehealth condition of the human subject, in accordance with the pressureanalysis of the system aspect as described above. Consequently, inanother embodiment, a subtype of rhinitis is detected by determiningwhether any individual values of any one of the curve propertiessurpasses a predetermined threshold_(max) for that particular curveproperty. Similarly, in another embodiment, a subtype of rhinitis isdetected by determining whether any individual values of any one of thecurve properties goes below a predetermined threshold_(min) for thatparticular curve property.

As part of the analyzing described above, a reference pressure curve maybe provided and the measured pressure curve may be compared to thereference pressure curve. The reference pressure curve may be selectedfrom a previously obtained measured pressure curve; an average of atleast two previously obtained measured pressure curves; a fit of a modelto at least one measured pressure curve, or a theoretically calculatedreference pressure curve, in accordance with the description inconnection to the first method aspect. The comparison between themeasured pressure curve and the reference pressure curve may be done inorder to either determine whether the measured pressure curvecorresponds to the reference pressure curve or lies within apredetermined tolerance interval; determine whether at least parts ofthe measured pressure curve exceed the tolerance interval, or determinewhether at least parts of the measured pressure curve fall below thetolerance interval.

In another embodiment, said creating of a measured pressure curvecomprises either storing time and pressure value pairs or fitting amodel to time and pressure value pairs.

The measured pressure curve may thus be obtained from pressuremeasurements conducted in the nasal cavity of a human subject. Inaddition to the pressure measurements conducted in the nasal cavity, themethods may further comprise imparting vibrations to the tissue in thenasal cavity via the inflatable member. By conducting vibrationstimulation in the nasal cavity at the same time as the pressure exertedby tissue on the inflatable member is measured, the measured pressurewill not only provide information on a subject's health condition, butalso information on tissue compliance to imparted vibrations. Therefore,in another embodiment of the method aspects, the methods comprisedetermining compliance of the tissue to the imparted vibrations.

In yet another embodiment, the methods comprise detecting peakscorresponding to sneezes in the tissue response pressure curve or in thepressure exerted on the inflatable member. As previously discussed,should the peak frequency surpass a predetermined peak threshold, thismay be an indication of a particular health condition of the humansubject.

When expanded within the nasal cavity, an inflatable member may abutagainst the tissue of the nasal cavity at a pressure of betweenapproximately 100 and 180 mbar, for instance from 120 to 160 mbar, suchas from 130 to 150 mbar. This corresponds to the pressure applied wheninitiating the pressure measurements in the nasal cavity.

Pressure measurements may conveniently be conducted in the nasal cavityduring a time period of between approximately 1 and 10 minutes.

In particular embodiments of the method aspect, the inflatable membermay be comprised within a device or a system as defined in the deviceand system aspects of the present invention.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus are not limitativeof the present invention, and wherein:

FIG. 1 is a schematic representation depicting an example of a deviceaccording to the device aspect of the present invention;

FIG. 2 is a schematic view depicting an example of a system according tothe system aspect of present invention;

FIG. 3 is a flow chart indicating the steps comprised in one embodimentof a tissue response pressure analyzing method according to the presentinvention; and

FIG. 4 is a pressure curve showing exemplary measured tissue responsepressure curves a)-c) representative of different health conditions.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will now be described with reference to theaccompanying drawings, wherein the same or similar elements areidentified with the same reference numeral.

With reference to FIG. 1, a specific example of a device according tothe device aspect of the present invention will now be discussed. Thedevice 1 for detection of rhinitis in a human subject has twoconfigurations, or states, wherein FIG. 1 depicts a secondconfiguration, or state, of the device. The inflatable member 2 is, inits expanded state, arranged to partly surround an expansion member 3,such that the end portion of the expansion member 3 is located insidethe inflatable member 2. The inflatable member 2 is for example aballoon made of a material such as plastic or rubber. In some instances,the inflatable member is made of latex.

The expansion member 3 comprises at least one channel 4 for supply offluid to the inflatable member 2. The inflatable member 2 thus comprisesa chamber for containing fluid, e.g. gas or liquid, supplied by theexpansion member 3. The chamber walls are defined by the inner surfaceof the inflatable member 2. The supply of fluid to the inflatable member2 via the expansion member 3 thus influences the volume and degree ofexpansion of the inflatable member 2. To allow free passage of fluidfrom the expansion member 3 to the inflatable member 2, the end portion3 a of the expansion member 3 comprises at least one opening 3 b. If theend portion 3 a of the expansion member 3 is arranged freely within theinflatable member 2, as for example depicted in FIG. 1, the end portion3 a may comprise more than one opening 3 b for supply of fluid to theinflatable member 2. The opening(s) 3 b can be arranged around aperimeter of the end portion 3 a of the expansion member 3 and/or can bearranged in an axial direction at the terminus of end portion 3 a of theexpansion member 3. The opening(s) 3 b can be distributed along alongitudinal direction of the portion of the expansion member 3 that islocated within the inflatable member 2. Examples of an expansion membercomprising at least one channel 4 include a pipe, a tubing, a conduit, acylinder, a tube, etc. The expansion member 3 may for instance be madeof a plastic, rubber or metal material.

Alternative arrangements of an inflatable member 2 and an expansionmember 3 are anticipated, wherein the inflatable member 2, for exampleis connected adjacent to the end portion 3 a of the expansion member 3or arranged as a sleeve around the expansion member 3 some distance awayfrom the end portion 3 a. The parts of the expansion member 3 andinflatable member 2 in contact with the human body typically define aclosed system to prevent leakage of fluid to the human body.

Two pressure sensors 5 are optionally arranged on the outer surface ofthe inflatable member 2. This arrangement of pressure sensors 5 enablesaccurate measuring of a tissue response pressure as exerted on thesurface of the inflatable member 2 when the inflatable member 2 isarranged in its second expanded state within the nasal cavity of a humansubject. In this example of a device 1, two pressure sensors 5 arepresent, however, it should be understood that the device 1 may compriseany suitable number of pressure sensors 5, such as a plurality ofpressure sensors 5 arranged around the circumference of the inflatablemember. One example of a pressure sensor 5 that may be arranged on thesurface of the inflatable member is a strain gauge. Such a strain gaugemay be applied onto the surface, e.g. with glue or by evaporation.

Alternatively, a pressure sensor 5 may be integrated within theinflatable member 2. The pressure inside the inflatable member 2 isproportional to the pressure exerted by the tissue onto the outersurface of the inflatable member 2 and a pressure sensor 5 may thusmeasure the inner pressure of the inflatable member 2. One example of anintegrated pressure sensing member is a MEMS (Micro-Electro-MechanicalSystem) device.

Expansion of the inflatable member 2 may, for example be achieved byincreasing the air pressure within the inflatable member 2. Theexpansion member 3 may comprise a pressure generator, e.g. a syringe, aballoon, or a pump, arranged to increase the air pressure within theinflatable member. In such cases, the tissue response pressure may bemeasured by monitoring the air pressure within the inflatable member 2.A pressure sensor 5 may for example be arranged externally of theinflatable member 2 and in fluid communication with the channel 4. Amanually operated pumping bulb equipped with a manometer and a closingvalve may be used as a pressure generator. An exemplary mode ofoperation is to inflate the inflatable member 2 to a pressure in therange of 100 to 180 mbar by manually squeezing the pumping bulb, closingthe valve, and observing the time evolution of the air pressure withinthe inflatable member 2 as shown on the manometer.

In some examples, vibrations may be applied by changing the air volumewithin the device 1. The tissue response pressure as registered by thepressure sensors 5 can thus give an estimate of the compliance of thetissue surrounding the inflatable member 2. This may give an indicationon how the human subject in question would respond to a rhinitistreatment, e.g. a vibrational rhinitis treatment as disclosed in WO2008/138997.

In other examples of a rhinitis detection device, other types of sensingelements can be integrated in the device. The inflatable member 2 can,for example be provided with separate sensors 5 a for either one oftemperature, pH, and/or electrical conductivity. Such sensors can beattached to the outside surface of the inflatable member 2 or beintegral with the inflatable member 2 as described above with regard tothe pressure sensors 5. By receiving such data in addition to themeasured pressure, further characterization of nasal pathology may bepossible.

Referring to FIG. 2, the device 1 may further comprise a display member18 configured to display the pressure measured by the pressure sensingmember, i.e. the tissue response pressure. The display member can be anLCD panel, which can be separate from or part of the control unit 13.The display member 18 facilitates monitoring of the tissue responsepressure by an operator. Such display member 18 may either show acurrent value of the tissue response pressure only, or may alternativelyor also show how the tissue response pressure develops over time. Inother words the display member 18 is in one embodiment configured todisplay the pressure measured by the pressure sensing member as afunction of time. The display member may be digital or analog. In casethe display member only shows a current value of the tissue responsepressure the operator has to monitor the time development of the signalin order to be able to draw any conclusions regarding the nasalpathology. If the development of the tissue response pressure over timeis shown, e.g. on a computer screen or on an XY-plotter, the evaluationof nasal pathology for the operator is facilitated. In both caseshowever, it is the operator who, based on experience and/or training,draws conclusions regarding the health of the patient.

With reference to FIG. 2, a specific example of a system according tothe system aspect of the present invention will now be discussed. Thesystem comprises a device 1 having an inflatable member 2 optionallyprovided with pressure sensors 5 at the surface. The inflatable member 2is arranged around an expansion member 3 as described above. Fluid suchas air enters the system via an inlet 6. In a pressure regulator 7, thefluid is pressurized before being supplied to the device 1 via tubing 8.One example of a pressure regulator 7 is a pressure pump. Before supplyto the device 1, the fluid may optionally pass a frequency and amplituderegulator 9. One example of a frequency and amplitude regulator 9 is anoscillation pump. If present, the frequency and amplitude regulator 9provides vibrations having a desired frequency and amplitude to thepressurized fluid, which subsequently via tubing 10 and expansion member3 is supplied to the device 1. Tubing 10 is provided with a safety valve11 for releasing fluid should the pressure within the inflatable member2 exceed a certain maximum value. For controlling the system pressure,and in some instances measure the inner pressure of the inflatablemember 2 representing the tissue response pressure, an external pressuresensor 12 may be provided.

The control unit 13 comprises a data collection module (not shown) forobtaining an input signal reflecting a measure of the tissue responsepressure exerted on the inflatable member 2 of the device 1 according tothe invention. The control unit 13 may in some embodiments receive theinput signal via line 17 from the pressure sensors 5 arranged on thedevice 1. The pressure exerted by the nasal tissue onto the inflatablemember 2 may be monitored continuously or according to a predeterminedschedule. The measured pressure may furthermore be stored in the datacollection module.

In addition, the system may comprise a display member 18 that isconfigured to display the pressure measured by the pressure sensors 5.The display member 18 may be integrated with control unit 13, as shownin FIG. 2, or may be arranged as a separate unit. The display member 18may be configured to display the pressure measured by the pressuresensing member as a current value, as a distinct value at a certain timepoint, or as a function of time.

The measured pressure is further analyzed by a pressure analyzing module(not shown), optionally arranged within the control unit 13. Thepressure analyzing module identifies plateaus and decreases in themeasured pressure signal, collected for example during a period of from1 to 10 minutes.

A rhinitis detection module (not shown) is further provided forcomparison of identified plateaus and decreases in the measured pressureto e.g. a predetermined boundary condition or to a reference pressurecurve. Rhinitis is hence detected.

The control unit 13 of the system is further connected to the pressureregulator 7 via line 14. Information regarding the applied pressure isthus forwarded from the pressure regulator 7 to the control unit 13 viasaid line 14. The application of pressure may in addition be centrallycontrolled from control unit 13.

If present, the frequency and amplitude regulator 9 communicates withthe control unit 13 via line 15. Information is forwarded from theoptional frequency and amplitude regulator 9 to the control unit via theline 15, and commands are transmitted from the control unit 13 to thefrequency and amplitude regulator 9 via said line 15.

It should be understood that the data collection module, the pressureanalyzing module and the rhinitis detection module may be integratedwithin a common control unit 13 as described above, or can be arrangedseparately from each other in, e.g. separate control units.

One example of a control unit 13 is a microprocessor comprising suitableperipheral I/O capability executing software, e.g. for analyzing theinput signal and for determining how to adjust the pressure andoptionally the frequency and the amplitude. It is contemplated thatother types of a control unit 13 may be used, such as e.g. a personalcomputer.

With reference to FIG. 3, a specific example of a method according to amethod aspect of the present invention will now be discussed. A tissueresponse pressure curve is firstly provided. The tissue responsepressure curve reflects the tissue response pressure of the nasal cavityof a human subject over a period of time. The tissue response pressurehas thus been measured and collected separately from the currentexemplary method. In other exemplary methods, an input signal reflectinga tissue response pressure is obtained and a tissue response pressurecurve is created by adapting a curve to individual values of the inputsignal obtained over a period of time, or by sampling said input signalover a period of time. By adapting a curve to the individual values, thecomparison to a reference curve may be easier to perform, especially ifthe reference curve is formulated in the same way. This can furthermorebe an efficient way to remove noise from the signal. Use of sampledvalues eliminates the need for a parameterized representation.

A reference pressure curve is thereafter provided. This referencepressure curve reflects a reference tissue response pressure of thenasal cavity over a reference period of time. This reference pressurecurve can be obtained according to procedures described herein.

Subsequently, the curves are compared. The tissue response pressurecurve is compared to said reference pressure curve in order to assesscorrespondence between the two. The comparison may be of relevance for asubsequent detection step wherein rhinitis is detected by, e.g.determining whether there is correspondence or whether the tissueresponse pressure curve lies within a predetermined tolerance interval;determining whether at least parts of the tissue response pressure curveexceeds said tolerance interval, and determining whether at least partsof the tissue response pressure curve falls below said toleranceinterval.

Rhinitis Detection in Human Subjects

By applying a static pressure in a balloon inserted into the nasalcavity and monitoring the resulting pressure over time, rhinitis can bedetected. Observations from tissue response pressure measurements in thenasal cavities of human patients are accounted for in the following.

The patients subjected to the measurements have been categorized intothree general groups, B), C) and D). The first group A) representshealthy patients (i.e. not suffering from rhinitis).

The second group B) represents patients suffering from a subtype ofrhinitis. This group of patients is commonly referred to as blockers.Blockers experience a stuffy nose, sometimes in combination withsneezes. These patients have typically been treated with pharmaceuticals(e.g. cortisone) with a success rate below 50% in the non-allergiccases. An alternative treatment option is invasive tissue destructivesurgery. This group constitutes about 80% of the rhinitis patients.

The third group C) also represents patients suffering from a subtype ofrhinitis, and this group is commonly referred to as sneezers. Sneezers,as the name implies, sneeze a lot. Sneezing is often accompanied byincreased secretion in the nose. This group constitutes about 10% of therhinitis patients.

The fourth group D) also represents patients suffering from a subtype ofrhinitis. This group is commonly denoted runners. Typical symptomsinclude a lot of secretion in the nose. The runners represent theremaining 10% of the rhinitis patients and are the most problematic totreat. There are most likely several pathologies contributing to thistype of syndrome, for instance connected to aging. These patients areoften therapy resistant.

In FIG. 4 representative tissue response pressure curves are shown,wherein a) represents the healthy group A), b) represents the blockersB) and c) represents the sneezers c).

The inflatable member used was a balloon which in an expanded state hada diameter of approximately 1.5 cm and a length of 5 cm. The balloon wasconnected with a tubing having a length of approximately 15 cm. Thetubing and the balloon were connected to each other such that one end ofthe tubing resided within the balloon, having a length of maximally 4 cmto simplify introduction into the nasal cavity. The tubing supplied airto the balloon for expanding the same. The other end of the tubing wasconnected via a three-way cock to a graduated syringe (20 ml) as well asto another tubing, which was connected to a closed air system.

The closed air system was connected to a flexible membrane, which duringsome pressure measurements was oscillated with a variable frequency inthe interval 10-100 Hz by means of a motor. The air pressure could bevaried in a controlled manner within a pressure interval of 5-180 mbar.The amplitude of the oscillating membrane could be varied in acontrolled manner (in arbitrary but reproducible units). Prior to use,the balloon was provided with a hygienic protective cover, consisting ofa finger from a disposable glove. The hygienic protective cover wasdipped in a paraffin solution prior to each introduction into a nasalcavity.

It was discovered that in a human patient representing group A), thepressure initially dropped to a level of about 100 mbar. Thereaftersudden pressure decreases of approximately 10 mbar were observed. Thepressure decreases occurred repeatedly with periods of nearly constantpressure in between. The decreases were observed at increasing timeintervals of about 10 seconds. After a period of approximately 1 minute,a first saturation pressure was reached wherein the measured pressurewas in the range of from 25 to 30 mbar. The applied pressure was thenlowered to approximately 5 mbar. Following a smooth recovery, themeasured tissue pressure was stabilized at a second saturation pressureof approximately 15 mbar.

The interpretation of pressure measurements on healthy persons of groupA) is that the sudden pressure decreases correspond to sphinctersopening up which leads to less blood filling in the nasal mucosa. Thesmooth recovery seen after the deliberate pressure decrease is in turnbelieved to correspond to refilling of the vessels and resumed functionof the sphincters.

In the second group B), the initial pressure decrease was slowercompared to the healthy reference, see FIG. 4 b). This was followed byrelatively small decreases in pressure and sometimes relatively longperiods of nearly constant pressure. These periods of nearly constantpressure are referred to as plateaus. The relatively small decreases andlong plateaus are hypothesized to be due to sphincters being stuck andunable to open in the way they do in healthy subjects.

In the third group C), tissue response pressure dropped comparativelyfast with relatively short plateau periods between the pressure drops.The reason for this might be that the sphincters could only withstandthe applied pressure for a short period of time.

In the fourth group D), tissue response pressure curves similar to thoseof group A) were observed. To distinguish this group of patients fromthe other groups, vibrations were administered via the inflatable memberto the nasal cavity in patients representing all the defined groups. Thevibrations immediately provoked reactions in the rhinitis patients butnot in the healthy humans. The reactions displayed by the rhinitispatients were, among others, frequent sneezing, increased secretion innose and/or eyes, itches and a sensation of stuffed nose in the cavitynot being subjected to vibrations. The healthy humans, on the otherhand, merely noted that vibrations were applied without showing anysigns of over sensibility. The initially strong reaction in the rhinitispatients to the applied vibrations subsequently diminished.

After being subjected to vibration administration, essentially asdescribed in WO 2008/138997, the rhinitis patients displayed the sametype of tissue response pressure curves as those of group A). It isbelieved that when the initially strong reaction of the rhinitispatients diminished, the patients were relieved of his/her symptoms.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention, and all suchmodifications as would be obvious to one skilled in the art are intendedto be included within the scope of the following claims.

What is claimed is:
 1. A method for detecting rhinitis, comprising thesteps of: introducing an inflatable member into a nasal cavity of ahuman subject; expanding the inflatable member within the nasal cavitysuch that the inflatable member abuts against a tissue of the nasalcavity; measuring a pressure exerted on the inflatable member by thetissue of the nasal cavity over a period of time to create a measuredpressure curve; analyzing the measured pressure curve to detectrhinitis, wherein the step of analyzing comprises the steps of:identifying plateaus and decreases in said measured pressure curve; andcomparing said plateaus and decreases to at least one predeterminedboundary condition; characterizing the plateaus and decreases by atleast one curve property selected from amplitude, rate of change orfrequency; and detecting a subtype of rhinitis, the step of detectingthe subtype of rhinitis comprising at least one of the followingsub-steps: determining whether any individual values of any one of thecurve properties surpasses a predetermined maximum threshold for thatparticular curve property, and determining whether any individual valuesof any one of the curve properties goes below a predetermined minimumthreshold for that particular curve property.
 2. The method according toclaim 1, wherein the analyzing comprises providing a reference pressurecurve and comparing the measured pressure curve to the referencepressure curve.
 3. The method according to claim 2, further comprisingone of determining whether the measured pressure curve corresponds tothe reference pressure curve or lies within a predetermined toleranceinterval; determining whether at least part of the measured pressurecurve exceeds the tolerance interval, or determining whether at leastpart of the measured pressure curve falls below the tolerance interval.4. The method according to claim 2, wherein the reference pressure curveis selected from a previously obtained measured pressure curve; anaverage of at least two previously obtained measured pressure curves; afit of a model to at least one measured pressure curve; or atheoretically calculated reference pressure curve.
 5. The methodaccording to claim 1, further comprising imparting vibrations to thetissue in the nasal cavity via the inflatable member.
 6. The methodaccording to claim 5 further comprising determining compliance of thetissue to the imparted vibrations.
 7. The method according to claim 5,further comprising detecting peaks corresponding to sneezes in thepressure exerted on the inflatable member.
 8. The method according toclaim 7, further comprising determining whether a peak frequencysurpasses a predetermined peak threshold.
 9. The method according toclaim 1, wherein the inflatable member abuts against the tissue of thenasal cavity at a pressure of between 100 and 180 mbar.
 10. The methodaccording to claim 1, wherein the period of time is between 1 and 10minutes.
 11. The method according to claim 1, wherein the measuredpressure curve is created by a method comprising either storing time andpressure value pairs or fitting a model to time and pressure valuepairs.
 12. The method according to claim 1, wherein the inflatablemember is present in a device, comprising: an inflatable member that, ina first state, is configured to be introducible into the nasal cavity ofthe human subject; an expansion member configured to expand theinflatable member to an expanded, second state within the nasal cavitysuch that the inflatable member abuts against the tissue of the nasalcavity.
 13. The method according to claim 12, wherein the device furthercomprises a pressure sensor configured to measure a pressure exerted onthe inflatable member by the tissue of the nasal cavity.
 14. The methodaccording to claim 12, wherein the expansion member further comprises atubular structure comprising an end portion arranged freely within saidinflatable member said end portion comprising at least one opening forfluid communication with the inflatable member.